Regulated Cell Death: Signaling and Mechanisms

2014 ◽  
Vol 30 (1) ◽  
pp. 337-356 ◽  
Author(s):  
Avi Ashkenazi ◽  
Guy Salvesen
2014 ◽  
Vol 26 (7) ◽  
pp. 3115-3131 ◽  
Author(s):  
Kira M. Veley ◽  
Grigory Maksaev ◽  
Elizabeth M. Frick ◽  
Emma January ◽  
Sarah C. Kloepper ◽  
...  

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 990
Author(s):  
Jean-Marie Ravel ◽  
L. Cristobal Monraz Gomez ◽  
Nicolas Sompairac ◽  
Laurence Calzone ◽  
Boris Zhivotovsky ◽  
...  

The processes leading to, or avoiding cell death are widely studied, because of their frequent perturbation in various diseases. Cell death occurs in three highly interconnected steps: Initiation, signaling and execution. We used a systems biology approach to gather information about all known modes of regulated cell death (RCD). Based on the experimental data retrieved from literature by manual curation, we graphically depicted the biological processes involved in RCD in the form of a seamless comprehensive signaling network map. The molecular mechanisms of each RCD mode are represented in detail. The RCD network map is divided into 26 functional modules that can be visualized contextually in the whole seamless network, as well as in individual diagrams. The resource is freely available and accessible via several web platforms for map navigation, data integration, and analysis. The RCD network map was employed for interpreting the functional differences in cell death regulation between Alzheimer’s disease and non-small cell lung cancer based on gene expression data that allowed emphasizing the molecular mechanisms underlying the inverse comorbidity between the two pathologies. In addition, the map was used for the analysis of genomic and transcriptomic data from ovarian cancer patients that provided RCD map-based signatures of four distinct tumor subtypes and highlighted the difference in regulations of cell death molecular mechanisms.


2021 ◽  
pp. 1-16
Author(s):  
Chandramani Pathak ◽  
Foram U. Vaidya ◽  
Bhargav N. Waghela ◽  
Abu Sufiyan Chhipa ◽  
Budhi Sagar Tiwari ◽  
...  

2018 ◽  
Vol 38 (01) ◽  
pp. 073-086 ◽  
Author(s):  
Lily Dara

AbstractThe receptor interacting serine/threonine kinase1 and 3 (RIPK1, RIPK3) are regulators of cell death and survival. RIPK1 kinase activity is required for necroptosis and apoptosis, while its scaffolding function is necessary for survival. Although both proteins can mediate apoptosis, RIPK1 and RIPK3 are most well-known for their role in the execution of necroptosis via the mixed lineage domain like pseudokinase. Necroptosis is a caspase-independent regulated cell death program which was first described in cultured cells with unknown physiologic relevance in the liver. Many recent reports have suggested that RIPK1 and/or RIPK3 participate in liver disease pathogenesis and cell death. Notably, both proteins have been shown to mediate inflammation independent of cell death. Whether necroptosis occurs in hepatocytes, and how it is executed in the presence of an intact caspase machinery is controversial. In spite of this controversy, it is evident that RIPK1 and RIPK3 participate in many experimental liver disease models. Therefore, in addition to cell death signaling, their necroptosis-independent role warrants further examination.


Marine Drugs ◽  
2019 ◽  
Vol 17 (2) ◽  
pp. 76 ◽  
Author(s):  
Esther Guzmán

Our understanding of cell death used to consist in necrosis, an unregulated form, and apoptosis, regulated cell death. That understanding expanded to acknowledge that apoptosis happens through the intrinsic or extrinsic pathways. Actually, many other regulated cell death processes exist, including necroptosis, a regulated form of necrosis, and autophagy-dependent cell death. We also understand that apoptosis occurs beyond the intrinsic and extrinsic pathways with caspase independent forms of apoptosis existing. Our knowledge of the signaling continues to grow, and with that, so does our ability to target different parts of the pathways with small molecules. Marine natural products co-evolve with their targets, and these unique molecules have complex structures with exquisite biological activities and specificities. This article offers a review of our current understanding of the signaling pathways regulating cell death, and highlights marine natural products that can affect these signaling pathways.


2021 ◽  
Vol 11 ◽  
Author(s):  
Thibault Roudaire ◽  
Marie-Claire Héloir ◽  
David Wendehenne ◽  
Aymeric Zadoroznyj ◽  
Laurence Dubrez ◽  
...  

Both plants and animals are endowed with sophisticated innate immune systems to combat microbial attack. In these multicellular eukaryotes, innate immunity implies the presence of cell surface receptors and intracellular receptors able to detect danger signal referred as damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs). Membrane-associated pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs), C-type lectin receptors (CLRs), receptor-like kinases (RLKs), and receptor-like proteins (RLPs) are employed by these organisms for sensing different invasion patterns before triggering antimicrobial defenses that can be associated with a form of regulated cell death. Intracellularly, animals nucleotide-binding and oligomerization domain (NOD)-like receptors or plants nucleotide-binding domain (NBD)-containing leucine rich repeats (NLRs) immune receptors likely detect effectors injected into the host cell by the pathogen to hijack the immune signaling cascade. Interestingly, during the co-evolution between the hosts and their invaders, key cross-kingdom cell death-signaling macromolecular NLR-complexes have been selected, such as the inflammasome in mammals and the recently discovered resistosome in plants. In both cases, a regulated cell death located at the site of infection constitutes a very effective mean for blocking the pathogen spread and protecting the whole organism from invasion. This review aims to describe the immune mechanisms in animals and plants, mainly focusing on cell death signaling pathways, in order to highlight recent advances that could be used on one side or the other to identify the missing signaling elements between the perception of the invasion pattern by immune receptors, the induction of defenses or the transmission of danger signals to other cells. Although knowledge of plant immunity is less advanced, these organisms have certain advantages allowing easier identification of signaling events, regulators and executors of cell death, which could then be exploited directly for crop protection purposes or by analogy for medical research.


2020 ◽  
Author(s):  
Claire DELEHOUZÉ ◽  
Arnaud COMTE ◽  
Marcelle HAUTEVILLE ◽  
Peter G GOEKJIAN ◽  
Marie-Thérèse DIMANCHE-BOITREL ◽  
...  

Nigratine (also known as 6E11), a natural flavanone derivative, was characterized as highly specific non-ATP competitive inhibitor of RIPK1 kinase, one of the key component of necroptotic cell death signaling. We show here that nigratine inhibited both necroptosis (induced by Tumor Necrosis Factor-alpha) and ferroptosis (induced by glutamate, erastin or RSL3 small chemical compounds) with EC50 in the microM range. Altogether, the data obtained showed that nigratine is the first-in-class dual inhibitor of necroptosis and ferroptosis cell death routes and opened new therapeutic avenues for treating complex necrosis-related diseases.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Joanna L. Fox ◽  
Michelle A. Hughes ◽  
Xin Meng ◽  
Nikola A. Sarnowska ◽  
Ian R. Powley ◽  
...  

AbstractRegulated cell death is essential in development and cellular homeostasis. Multi-protein platforms, including the Death-Inducing Signaling Complex (DISC), co-ordinate cell fate via a core FADD:Caspase-8 complex and its regulatory partners, such as the cell death inhibitor c-FLIP. Here, using electron microscopy, we visualize full-length procaspase-8 in complex with FADD. Our structural analysis now reveals how the FADD-nucleated tandem death effector domain (tDED) helical filament is required to orientate the procaspase-8 catalytic domains, enabling their activation via anti-parallel dimerization. Strikingly, recruitment of c-FLIPS into this complex inhibits Caspase-8 activity by altering tDED triple helix architecture, resulting in steric hindrance of the canonical tDED Type I binding site. This prevents both Caspase-8 catalytic domain assembly and tDED helical filament elongation. Our findings reveal how the plasticity, composition and architecture of the core FADD:Caspase-8 complex critically defines life/death decisions not only via the DISC, but across multiple key signaling platforms including TNF complex II, the ripoptosome, and RIPK1/RIPK3 necrosome.


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